The cutaneous tissue contains cellular protein and glycoprotein components which together influence the thickness and form of the tissue. Fibroblasts are a common cellular constituent of the skin and produce various proteins that are important structural components of cutaneous tissue. One such protein is collagen which can be and is widely used to artificially augment cutaneous shape. A characteristic of ageing and wrinkled skin is a reduction in cellularity. A potential goal of treating ageing or wrinkled skin could be to increase the cellularity in an affected area of skin. A further desirable effect of an increase in cellularity may be increased production of extracellular dermal components, including for example, collagen.
One of the clinical features of treating damaged skin with retinoic acid, believed to be of cosmetic benefit, is an increase in new collagen synthesis. Another commonly used treatment for skin wrinkling, glycolic acid, has been shown to increase collagen synthesis in fibroblast cultures in vitro and it has been suggested that this effect may occur in vivo and account for the apparent beneficial effects associated with glycolic acid use. It has also been proposed that a deficiency of superficial dermal collagen is the main cause of photo-ageing.
U.S. Pat. No. 5,980,916 describes the use of laminarin or laminarin-derived oligosaccharides as a “cosmetic or pharmaceutical, particularly dermatological”. Laminarin is a polysaccharide derived from Laminaria spp seaweed and is a linear polymer composed of beta-1,3-D-glucose and a small amount of beta-1,6-D-glucose linkages. This patent describes laminarin, oligosaccharides derived therefrom, and compositions containing these substances as having stimulating, regenerating, conditioning and energising effects on human dermis fibroblasts and human epidermis keratinocytes. It does not teach or suggest the use of any oligosaccharides or polysaccharides other than those from laminarin as a means for stimulating skin cells (eg, fibroblasts and keratinocytes).
U.S. Pat. No. 5,916,880 describes the use of a sulphate saccharide or a salt or complex thereof for the preparation of a medicament for topical application to the skin. This patent also describes a method for cosmetically treating skin to reduce wrinkles, the method comprising topically applying to affected areas of skin a cosmetically effective amount of at least one compound selected from the group consisting of sulfate monosaccharides, sulfate disaccharides, and salts and complexes thereof. U.S. Pat. No. 5,916,880 does not disclose the use of any agents other than sulfate sugars for the treatment of skin wrinkles. U.S. Pat. No. 5,916,880 states that the saccharide is preferably a polysulphated or persulphated saccharide, which means that two or more, possibly all, sulphur-containing moieties are present as substituents on the carbohydrate moiety. The compounds and methods disclosed in this patent do not teach or imply that non-sulfated oligosaccharides or polysaccharides could have a skin augmenting or tissue regeneration activity.
WO 03/068243 and corresponding Australian patent No. 2003245471 describe oligosaccharides and polysaccharides based either on glucose or mannose, but not both, which have skin augmenting activity. Glucose based oligosaccharides or polysaccharides described are amylopectin, amylose, 1,4-D-glucose oligosaccharides isolated by acid hydrolysis of amylose, maltopentaose, maltohexaose, maltoheptaose, alpha-1′,4-maltooctaose, maltononaose, maltodecanose, maltoundecanose and maltododecanose. Mannose based oligosaccharides or polysaccharides described include 1,4-beta-D-mannose oligosaccharides and polysaccharides, the latter being commonly referred to as 1,4-beta-D-mannans. Other materials described include the 1,4-beta-D-mannose polymer isolated from the seeds of Phoenix canariensis and the oligosaccharides isolated therefrom. 1,4-Beta-D-mannose oligosaccharides of from 4 to 12 mannose units are described, as is mannan from Saccharomyces cerevisiae; exocellular phosphomannan produced by Pichia holstii, purified D-mannose high molecular weight acid-resistant polysaccharide core of the exocellular phosphomannan produced by Pichia holstii; 6-O-phospho-alpha-D-mannose-(1,3)-alpha-D-mannose-(1,3)-alpha-D-mannose-(1,3)-alpha-D-mannose-(1,2)-alpha-D-mannose, beta-1,4-mannopentaose, beta-1,4-mannohexaose; beta-1,4-mannoheptaose, beta-1,4-mannooctaose, beta-1,4-mannononaose, beta-1,4-mannodecanose, beta-1,4-mannoundecanose and beta-1,4-mannododecanose.
WO 03/068243 does not describe glucomannan oligosaccharides or polysaccharides, or any oligosaccharides or polysaccharides based on both glucose and mannan, as is glucomannan. The compounds and methods disclosed in WO 03/068243 also do not teach or suggest that oligosaccharides or polysaccharides based on both glucose and mannan, such as glucomannan, could have skin regeneration, wound healing or skin augmenting properties.
Glucomannan is most commonly derived from konjac root (Amorphophallus konjac). Amorphophallus konjac is a perennial herbaceous herb. It grows in mountain or hilly areas in subtropical regions mainly in the South East of Asia. It has been used as a food and food additive in China and Japan for more than 1000 years. The fresh konjac tuber contains an average of 13% dry matter. Sixty four percent of the dry matter is glucomannan and 30% is starch. The molecular mass of glucomannan derived from the konjac tuber is 200,000 to 2,000,000 Da, depending upon konjac species or variety and processing method. Glucomannan can absorb up to 200 times its weight in water. Glucomannan from the konjac tuber is relatively inexpensive and readily available, particularly in comparison with the agents listed in WO 03/068243.
Glucomannan derived from the konjac root is a high molecular weight polysaccharide formed from residues of glucose (G) and mannose (M) in a proportion of 5:8 bound together by β-1,4-linkages. The basic polymeric repeating unit has the pattern: GGMMGMMMMMGGM. Glucomannan is not a linear molecule and has short side chains of 11-16 monosaccharides occurring at intervals of 50-60 units of the main chain attached by 1β→3 linkages. Acetyl groups on carbon 6 are located on every 9-19th sugar unit of the main chain. These acetyl groups contribute to the solubility and gelling properties. If the acetyl groups are removed under mild alkaline conditions, the molecule will produce heat stable gels. Glucomannans from other sources may contain glucose and mannose in different proportions and/or different sequences, as well as minor amounts of sugars other than glucose and mannose. All such forms of glucomannan are encompassed by the present invention.
Konjac glucomannan as a food additive is approved in Canada by Health Canada, is FDA approved as GRAS in the United States and is approved by the EU under E425, Annex V, food additives, 1998, EU.
The present inventor has found that glucomannan (oligosaccharides and polysaccharides) has skin regeneration, wound healing and skin augmenting activity.